Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo

Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transac...

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Autores principales: Cardo, Lucia, Nawroth, Isabel, Cail, Peter J., McKeating, Jane A., Hannon, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127258/
https://www.ncbi.nlm.nih.gov/pubmed/30190568
http://dx.doi.org/10.1038/s41598-018-31513-3
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author Cardo, Lucia
Nawroth, Isabel
Cail, Peter J.
McKeating, Jane A.
Hannon, Michael J.
author_facet Cardo, Lucia
Nawroth, Isabel
Cail, Peter J.
McKeating, Jane A.
Hannon, Michael J.
author_sort Cardo, Lucia
collection PubMed
description Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity with limited evidence of cellular cytotoxicity. These metallo-supramolecular compounds provide an exciting avenue for developing a new class of anti-viral agents.
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spelling pubmed-61272582018-09-10 Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo Cardo, Lucia Nawroth, Isabel Cail, Peter J. McKeating, Jane A. Hannon, Michael J. Sci Rep Article Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity with limited evidence of cellular cytotoxicity. These metallo-supramolecular compounds provide an exciting avenue for developing a new class of anti-viral agents. Nature Publishing Group UK 2018-09-06 /pmc/articles/PMC6127258/ /pubmed/30190568 http://dx.doi.org/10.1038/s41598-018-31513-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cardo, Lucia
Nawroth, Isabel
Cail, Peter J.
McKeating, Jane A.
Hannon, Michael J.
Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title_full Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title_fullStr Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title_full_unstemmed Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title_short Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
title_sort metallo supramolecular cylinders inhibit hiv-1 tar-tat complex formation and viral replication in cellulo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127258/
https://www.ncbi.nlm.nih.gov/pubmed/30190568
http://dx.doi.org/10.1038/s41598-018-31513-3
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